Identification

Name
Zomepirac
Accession Number
DB04828
Type
Small Molecule
Groups
Withdrawn
Description

Zomepirac, formerly marketed as Zomax tablets, was associated with fatal and near-fatal anaphylactoid reactions. The manufacturer voluntarily removed Zomax tablets from the Canadian, US, and UK markets in March 1983.

Structure
Thumb
Synonyms
  • 5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetic acid
  • Zomepiracum
Product Ingredients
IngredientUNIICASInChI Key
Zomepirac sodiumY0185WZ20964092-49-5ZJXLSCXDGPDZOL-UHFFFAOYSA-M
Zomepirac sodium anhydrousDA5B6IWF4664092-48-4SEEXPXUCHVGZGU-UHFFFAOYSA-M
Categories
UNII
822G987U9J
CAS number
33369-31-2
Weight
Average: 291.73
Monoisotopic: 291.066221026
Chemical Formula
C15H14ClNO3
InChI Key
ZXVNMYWKKDOREA-UHFFFAOYSA-N
InChI
InChI=1S/C15H14ClNO3/c1-9-7-12(8-13(18)19)17(2)14(9)15(20)10-3-5-11(16)6-4-10/h3-7H,8H2,1-2H3,(H,18,19)
IUPAC Name
2-[5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]acetic acid
SMILES
CN1C(CC(O)=O)=CC(C)=C1C(=O)C1=CC=C(Cl)C=C1

Pharmacology

Indication

Zomepirac was indicated for the management of mild to severe pain.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UProstaglandin D2 receptor 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when Zomepirac is combined with (4R)-limonene.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Zomepirac is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Zomepirac is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Zomepirac is combined with 5-androstenedione.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Zomepirac is combined with Abciximab.
AcebutololZomepirac may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Zomepirac is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Zomepirac is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Zomepirac is combined with Acenocoumarol.
AcetaminophenZomepirac may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

James B. Doherty, Debra L. Allison, "Process for the preparation of zomepirac and related compounds." U.S. Patent US4374997, issued January, 1978.

US4374997
General References
Not Available
External Links
PubChem Compound
5733
PubChem Substance
46504549
ChemSpider
5531
BindingDB
50027952
ChEBI
35859
ChEMBL
CHEMBL19490
PharmGKB
PA166049188
HET
ZOM
Wikipedia
Zomepirac
ATC Codes
M01AB04 — Zomepirac
PDB Entries
3r8h / 4jq3

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.026 mg/mLALOGPS
logP3.37ALOGPS
logP3.33ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.86ChemAxon
pKa (Strongest Basic)-7.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.3 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity77.2 m3·mol-1ChemAxon
Polarizability29.68 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9714
Blood Brain Barrier+0.8608
Caco-2 permeable+0.7695
P-glycoprotein substrateNon-substrate0.7316
P-glycoprotein inhibitor INon-inhibitor0.9347
P-glycoprotein inhibitor IINon-inhibitor0.9287
Renal organic cation transporterNon-inhibitor0.7965
CYP450 2C9 substrateNon-substrate0.7288
CYP450 2D6 substrateNon-substrate0.8163
CYP450 3A4 substrateNon-substrate0.5337
CYP450 1A2 substrateNon-inhibitor0.7776
CYP450 2C9 inhibitorNon-inhibitor0.8844
CYP450 2D6 inhibitorNon-inhibitor0.8955
CYP450 2C19 inhibitorNon-inhibitor0.7741
CYP450 3A4 inhibitorNon-inhibitor0.8973
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8525
Ames testNon AMES toxic0.8817
CarcinogenicityNon-carcinogens0.8425
BiodegradationNot ready biodegradable0.9476
Rat acute toxicity2.7638 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9389
hERG inhibition (predictor II)Non-inhibitor0.8816
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Benzoyl derivatives / Chlorobenzenes / N-methylpyrroles / Aryl chlorides / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
Aryl-phenylketone / Benzoyl / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Substituted pyrrole / N-methylpyrrole
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid, monochlorobenzenes, aromatic ketone, pyrroles (CHEBI:35859)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Prostaglandin j receptor activity
Specific Function
Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is al...
Gene Name
PTGDR2
Uniprot ID
Q9Y5Y4
Uniprot Name
Prostaglandin D2 receptor 2
Molecular Weight
43267.15 Da
References
  1. Hata AN, Lybrand TP, Marnett LJ, Breyer RM: Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol Pharmacol. 2005 Mar;67(3):640-7. Epub 2004 Nov 24. [PubMed:15563582]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Chen Q, Doss GA, Tung EC, Liu W, Tang YS, Braun MP, Didolkar V, Strauss JR, Wang RW, Stearns RA, Evans DC, Baillie TA, Tang W: Evidence for the bioactivation of zomepirac and tolmetin by an oxidative pathway: identification of glutathione adducts in vitro in human liver microsomes and in vivo in rats. Drug Metab Dispos. 2006 Jan;34(1):145-51. doi: 10.1124/dmd.105.004341. Epub 2005 Oct 26. [PubMed:16251255]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Pritchard JF, O'Neill PJ, Affrime MB, Lowenthal DT: Influence of uremia, hemodialysis, and nonesterified fatty acids on zomepirac plasma protein binding. Clin Pharmacol Ther. 1983 Nov;34(5):681-8. [PubMed:6627828]
  2. Ojingwa JC, Spahn-Langguth H, Benet LZ: Reversible binding of tolmetin, zomepirac, and their glucuronide conjugates to human serum albumin and plasma. J Pharmacokinet Biopharm. 1994 Feb;22(1):19-40. [PubMed:8027947]

Drug created on September 11, 2007 14:33 / Updated on September 15, 2018 18:17